Tin enolate derivative

More reactive anions, such as the very well studied enolate anions from ketones and esters, do not imdergo allylic alkylation except in special cases. Tin enolate derivatives are generally effective (equation 52). 

Alkyl-4-oxopentanals. In the presence of LiBr, the tin enolate derived from diketene and bis(tributyltin) oxide reacts with a-bromoaldehydes in a chemoselective manner. It involves displacement of the bromine and decarboxylation. 

Reductive aldol reactions/ In situ aldol reaction of the tin enolates derived from the reduction of enones provides a method for the preparation of p-hydroxy ketones with the 2,3-syn isomers predominating. 

TABLE 1. Pd-Catalyzed a-Arylation of Tin Enolates Derived from Methyl Ketones with Aryl Bromides in the Presence of Cl2Pd(o-ToljP)2 (cf. Scheme 8)... 

Scheme 28 shows a stereoselective epoxide synthesis, which proceeds by way of a tin enolate. Similarly, the tin enolates derived from triphenyltin chloride and lithium enolates, R HC=C(OLi)R react with alkyl and aryl aldehydes R CHO without the necessity for a catalyst to give mainly the erythro-products (139) in good yield. ... 

Scheme 3.6 Calculated relative energies of equilibrating O- and C-bound tautomers of tin enolates derived from acetophenone and methyl acetate.

The related serine derived (4S)-4-methoxycarbonyl-3-(l-oxopropyl)-2-thiono-l,3-oxazolidine 11, and the cysteine derived (4A)-4-methoxycarbonyl-3-(l-oxobntyl)-2-thiono-1,3-thiazolidine 13, also serve as efficient chiral auxiliaries in boron- and tin(II)-mediated aldol condensations98. Thus, conversion of 11 into the boron or tin enolate, followed by reaction with 2-methylpropanal affords predominantly one adduct. Subsequent methanolysis and chromatographic purification delivers the syu-methyl ester in 98% ee. 

Tin(Il) shows considerable affinity towards nitrogen, therefore is expected to activate the imino group. The diastereoselective addition of tin(II) enolates derived from thioesters 1 to x-imino-esters 2 is reported12. This reaction proceeds smoothly to afford. vi w-/j-amino acid derivatives 3 (d.r. 95 5) in good yields. Lithium, magnesium, and zinc enolates do not react while titanium enolates give the adducts in low yield with preferential formation of the anti-isomer. 

As an alternative, tin enolates are very useful in these additions. Usually they are prepared in situ from the amide using tin(II) trifluoromethanesulfonate and a base. They are subsequently reacted with an enone, catalyzed by a Lewis acid47-48 (see Table 3). With triinethylsilyl trifluoromethanesulfonate as a catalyst, in the presence of proline derived diamines anti-adducts are formed exclusively49 (see Section 1.5.2.4.3.1.). 

Organotin enamines can be prepared by treating organotin halides with the lithium or magnesium derivatives of enamines, and also by treating distannazanes with tin enolates (222,223). 

Among the preformed enol derivatives used in this way have been enolates of magnesium, lithium, titanium, zirconium, and tin, ° silyl enol ethers, enol borinates,and enol borates, R CH=CR"—OB(OR)2. The nucleophilicity of silyl enol ethers has been examined. In general, metallic Z enolates give the syn (or erythro) pair, and this reaction is highly useful for the diastereoselective synthesis of these products. The ( ) isomers generally react nonstereoselectively. However, anti (or threo) stereoselectivity has been achieved in a number of cases, with titanium enolates, with magnesium enolates, with certain enol bor-inates, and with lithium enolates at — 78°C. ... 

Reaction conditions that involve other enolate derivatives as nucleophiles have been developed, including boron enolates and enolates with titanium, tin, or zirconium as the metal. These systems are discussed in detail in the sections that follow, and in Section 2.1.2.5, we discuss reactions that involve covalent enolate equivalents, particularly silyl enol ethers. Scheme 2.1 illustrates some of the procedures that have been developed. A variety of carbon nucleophiles are represented in Scheme 2.1, including lithium and boron enolates, as well as titanium and tin derivatives, but in... 

In Step D another thiazoline chiral auxiliary, also derived from cysteine, was used to achieve double stereodifferentiation in an aldol addition. A tin enolate was used. The stereoselectivity of this reaction parallels that of aldol reactions carried out with lithium or boron enolates. After the configuration of all the centers was established, the synthesis proceeded to P-D lactone by functional group modifications. 

Several methods for the anti-selective, asymmetric aldol reaction recorded in the literature include (i) the use of boron, titanium, or tin(ll) enolate carrying chiral ligands, (ii) Lewis acid-catalyzed aldol reactions of a metal enolate of chiral carbonyl compounds, and (iii) the use of the metal enolate derived from a chiral carbonyl compound. Although many of these methods provide anti-aldols with high enantioselectivities, these methods are not as convenient or widely applicable as the method reported here, because of problems associated with the availability of reagents, the generality of reactions, or the required reaction conditions. 

Iwasawa and Mukaiyama have previously reported the first example of forming highly optically active aldols from aromatic ketones and various aldehydes, again via divalent tin enolates employing chiral diamines derived from (S)-proline as ligands 172>. 

Among the preformed enol derivatives used in this way have been enolates of magnesium, lithium,526 titanium,527 rhodium,528 zirconium,522 and tin,529 silyl enol ethers,530 enol bori-nates,531 and enol borates R CH=CR"—OB(OR)2.532 In general, metallic Z enolates give... 

These reactions can also be made enantioselective (in which case only one of the four isomers predominates) by using539 chiral enol derivatives,540 chiral aldehydes or ketones,541 or both.542 Since both new chiral centers are formed enantioselectively, this kind of process is called double asymmetric synthesis.543 A single one of the four stereoisomers has also been produced where both the enolate derivative and substrate were achiral, by carrying out the reaction in the presence of an optically active boron compound544 or a diamine coordinated with a tin compound.545... 

Enanantioselective aldol reactions. Divalent tin enolates of aldehydes and aryl ketones generated with tin(II) triflate undergo aldol condensation with aldehydes to form aldols.2 The reaction is highly enantioselective if conducted in the presence of chiral diamines derived from (S)-proline, such as l.3... 

The enolate can be built-in in the allyl esters of /3-keto esters (equation 53). The chemoselectivity is excellent, as shown by selective reaction of an allylic acetate in the presence of a simple ketone, using a tin enolate anion (equation 54). Even mildly nucleophilic species, such as allylic-tifr derivatives, react at room temperature, the method of choice for cross coupling of allylic units (equation 55). 

Subsequent deprotection and demetalation of (16) produced (—)-(1/f,8S)-1 -hydroxypyrrolizidin-3-one (17) (eq 11). Aldol condensation between the tin(II) and aluminum enolates derived from (2) and 2,3-isopropylidene-o-glyceraldehyde also proceeded with high stereoselectivity and the iron once again had the overwhelming directing effect on the stereochemical outcome of these condensations (eq 12). ... 

The tributyltin enolates 74 are readily prepared from the corresponding enol acetates and tributyltin methoxide in the absence of solvent [34]. The tin enolates thus obtained occur in the 0-Sn form and/or the C-Sn form, and both species can be used for the aldol reaction of this system. Although the tin enolates themselves have adequate reactivity toward aldehydes [34c], in the presence of the BINAP silver(I) catalyst the reaction proceeds much faster even at -20 °C. Optimum conditions entail the use of THF as solvent and the results employing these conditions in the catalytic enan-tioselective aldol reaction of a variety of tributyltin enolates with typical aromatic, a,/3-unsaturated, and aliphatic aldehydes are summarized in Table 2. TTie characteristic features are (i) All reactions proceed to furnish the corresponding aldol adducts 75 in moderate to high yield in the presence of 10 mol % (i )-BINAP AgOTf complex at -20 °C for 8 h, and no dehydrated aldol adduct is observed (ii) with an a,j3-unsaturated aldehyde, the 1,2-addition reaction takes place exclusively (entry 3) (iii) a bulky alkyl substituent of tin enolate increases the enantioselectivity of the aldol reaction. For instance, the highest ee (95 % ee) is obtained when the tin enolate prepared from pinacolone 77 or rert-butyl ethyl ketone 79 is added to aldehydes (entries 2, 7, and 8) (iv) addition of the cyclohexanone-derived enol tributylstannane 78 (( )-... 

The ultimate in the three-component coupling approach to prostaglandins has now been achieved by Noyori (48). As illustrated in Fig. 15, the cuprate derived from iodide [82] was added to enone [80] in the usual fashion. Then, after addition of hexamethylphosphoramide, triphenyltin chloride was used to effect enolate interchange. As opposed to lithium (or copper) enolates, the tin enolate is cleanly alkylated with allylic iodide [81]. The protected PGE2 [83] was obtained in 78% yield. Two-step deprotection to PGEj was straightforward. 

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